Premium
The bradykinin antagonist icatibant increases electrolyte and water excretion after sodium challenge in patients with liver cirrhosis
Author(s) -
Russmann S.,
Decosterd L.,
Buclin T.,
Schwaar T.,
Baumann S.,
BrunnerFerber F.,
Rosenkranz B.,
Knolle J.,
Reichen J.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.043
Subject(s) - icatibant , medicine , endocrinology , excretion , cirrhosis , antagonist , free water clearance , diuresis , renal function , chemistry , receptor
Purpose Patients with hepatic insufficiency are known to cope less efficiently with Na load. In a rat CCl 4 ‐induced liver cirrhosis model, Icatibant, a potent bradykinin‐2 receptor antagonist, prevented Na retention, improved diuresis, and reduced microvascular leakage (Wirth et al Eur J Pharmacol 1997; 37: 45–53). Methods : In a randomized, double‐blind, proof‐of‐concept study, 8 patients with liver cirrhosis (Child Pugh score 5‐8) and 8 healthy subjects on standardized diet received a constant 3 day infusion of Icatibant (0.15 mg/kg/day) or vehicle (placebo), with Na load on Day 2 (2L NaCl 0.9% i.v.). Results : Using sinistrine clearance, renal function did not change during treatment while the baseline extracellular body water (Vd) was higher in patients than volunteers (12.4 vs. 10.2 L/m 2 , p=0.05). In patients, 6‐12h after NaCl load, Icatibant increased Na excretion vs. placebo by 6.9 mmol/h (p=0.02), K excretion by 1.24 mmol/h (p=0.04), urine osmolarity by 18.54 mmol/h (p=0.01), and urine flow by 41.4 mL/h (p=0.05) while on Day 3 cumulative Na excretion was higher (+85.9 mmol, p=0.09) and body weight lower (−0.53 kg, p=0.04). In volunteers, response to Na load was prompt and nearly similar for both periods. Icatibant was safe and well tolerated. Conclusion : Icatibant increases the natriuretic response in cirrhotic patients after Na load. Its potential for treating patients with refractory ascites should be investigated further. Clinical Pharmacology & Therapeutics (2004) 75 , P12–P12; doi: 10.1016/j.clpt.2003.11.043